Thyroid nodules with ultrasound (US) cancer risk features and extra-thyroid lesions suggesting malignant lymph nodes, require prompt diagnosis, especially in children. The US pattern of intrathyroidal ectopic thymus (IET) can strongly suggest papillary thyroid carcinoma (PTC). The extra-thyroid ectopic thymic tissue (EET) can mimic pathological lymph nodes in US. The aim of the study has been to demonstrate US features and diagnostic methods, allowing finally to confirm the presence of IET and EET in children. The US and elastographic features of 16 ectopic thymic tissue (ET) lesions were analyzed so as to describe the typical characteristics of ET and to define the best method to differentiate ET and malignant lesions. Among 16 analyzed lesions, 11 lesions were IET, and 5 were EET adjacent to the thyroid connective tissue capsule. Most of IET were located in the middle part of the right lobe and were fusiform or oval in shape. All the lesions were solid, hypoechoic, and heterogeneous with bright internal echoes. Among IET, 73% of lesions had well- or very well-defined margins. In strain elastography of IET lesions, the strain ratio was similar in all lesions, and its value ranged from 0.95 to 1.09. Despite the low prevalence of IET and cervical EET, clinicians and radiologists should be aware of US characteristics of such lesions. The confirmation of their benign character is absolutely required. Elastography is a useful tool to initially differentiate PTC and IET. However, due to high risk of malignancy in thyroid lesions in children, similarity of US features of PTC and IET, and due to the possibility of malignancy in ET, only cytological evaluation provides definitive diagnosis.

BackgroundNormal thyroid hormone secretion or appropriate L-thyroxine (L-T4) substitution is necessary for the optimal effect of the growth hormone (GH) administration on growth rate. The decrease of free thyroxine (FT4) levels at recombinant human GH (rhGH) therapy onset has been reported in several studies. The aim of the present study was to evaluate the effect of rhGH administration on thyrotropin (TSH) and FT4 serum concentrations in children with GH deficiency (GHD) during the 1st year of therapy, as well as to assess potential indications to thyroid hormone supplementation in them.Patients and methodsThe analysis involved data of 75 children (59 boys, 16 girls) with disorders of GH secretion (GHD, neurosecretory dysfunction - NSD) and partial GH inactivity (inactGH), who were treated with rhGH for - at least - one year. In all the children, body height and height velocity (HV) were assessed before and after 1 year of therapy, while TSH, FT4, IGF-I and IGFBP-3 before treatment and after 3-6 months and 1 year of treatment. In the patients, who revealed hypothyroidism (HypoT), an appropriate L-T4 substitution was introduced immediately. The incidence of HypoT, occurring during the initial phase of rhGH therapy, was assessed, as well as its influence on the therapy effectiveness.ResultsBefore rhGH substitution, there were no significant differences in either auxological indices or TSH and FT4 secretion, or IGF-I concentration and its bioavailability among the groups of patients. During the initial 3-6 months of rhGH administration, a significant decrease of FT4 serum concentration, together with a significant increase of IGF-I SDS and IGF-I/IGFBP-3 molar ratio was observed in all the studied groups. In 17 children, HypoT was diagnosed and L-T4 substitution was administered. Despite similar IGF-I secretion increase, the improvement of HV presented significantly lower in children with HypoT than in those who remained euthyroid all the time.ConclusionsThe incidence of HypoT during the initial phase of GH treatment in children with GHD and the negative effect of even transient thyroid hormone deficiency on the growth rate should be taken into account.

Context Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). Objective Compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. Design 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study. Intervention Subjects were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. Patients or Other Participants 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). Main Outcome Measures The primary endpoint was annualized HV at month 12. Results HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: –0.24, 0.89). The lower bound of the two-sided 95% confidence interval was higher than the prespecified non-inferiority margin (–1.8 cm/year), demonstrating non-inferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height SDS at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon:78.9%, somatropin:79.1%). Conclusions The efficacy of once-weekly somatrogon was non-inferior to once-daily somatropin, with similar safety and tolerability profiles.

Background Some, however not all, children with growth hormone deficiency (GHD) reveal a tendency towards metabolic disorders. Insulin-like growth factor I (IGF-I) is the main mediator of GH anabolic effects. Objective The aim of the study was to compare ghrelin, adiponectin, leptin, resistin, lipid, glucose, and insulin concentrations in GHD children, depending on the IGF-I bioavailability. Methods The analysis comprised 26 children with GHD, aged 5.7–15.3 yrs. Fasting serum concentrations of IGF-I, IGFBP-3, ghrelin, leptin, adiponectin, resistin, lipids, glucose, and insulin were measured. The GHD children were divided into two subgroups: (1) with lower IGF-I/IGFBP-3 molar ratio and (2) with higher IGF-I/IGFBP-3 molar ratio. The control group consisted of 39 healthy children, aged 5.1–16.6 yrs, of normal height and body mass. Results GHD children with lower IGF-I/IGFBP-3 molar ratio were found to have a significantly lower body mass and insulin and triglyceride concentrations, as well as significantly higher ghrelin and adiponectin concentrations than GHD children with higher IGF-I/IGFBP-3. Conclusions A better metabolic profile characterised GHD children with low IGF-I bioavailability. This phenomenon may be the result of high adiponectin and ghrelin concentrations in those children and their influence on adipose tissue, glucose uptake, and orexigenic axis.

Introduction: Vitamin D 3 [25(OH)D] deficiency is a significant problem in Polish children. In many regions of the world, 25(OH)D concentrations show seasonal variation and differences between boys and girls, due to seasonal differences in insolation, as well as different sociological and cultural factors. The aim of the study was to assess the seasonal variations of 25(OH)D concentrations and the incidence of vitamin D deficiency in children from central Poland. Material and methods: The analysis comprised 1275 children, age 3-18 (11.2 ±4.0) years, with disorders of growing and/or puberty, obesity, and other complaints that could be related to endocrine diseases, except for ones with calcium-phosphorus imbalance, impaired parathyroid hormone secretion, and diseases that may influence vitamin D supply. Results: Seasonal variability of 25(OH)D concentrations was observed with maximal levels in August and minimal in January and close relationship between 25(OH)D levels and insolation in the previous two months. In all the quarters, 25(OH)D concentrations were lower in girls than in boys and in older vs. younger children. The median value of 25(OH)D concentrations was below the lower limit of optimal range during the whole year. High incidence of 25(OH)D deficiency was observed (from 10.7% in August to 80.4% in January) together with low proportion of normal 25(OH)D levels (from 3.6% in January to 42.1% in August). Conclusions: Our results are consistent with previous reports on inadequate vitamin D supplementation in Polish children and adolescents, pointing out the necessity to implement current recommendations concerning vitamin D supplementation and the need for further studies on the consequences vitamin D deficiency for health of children and adolescents, with special attention to the pleiotropic effects of vitamin D.

Context KIGS is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. Objective To evaluate the safety and efficacy of rhGH from the full KIGS cohort Design, Patients, Setting, and Intervention Data were collected by investigators from children with growth disorders treated with rhGH (Genotropin® [somatropin]; Pfizer, NY). Safety was evaluated in all treated patients, and efficacy in those treated for ≥1 year. A subgroup included patients treated for ≥5 years (≥2 years prepubertal) who had reached near-adult height (NAH). Main Outcomes Adverse events (AEs), serious AEs (SAEs), and height growth. Results The full KIGS cohort (N = 83,803 [58% male]) was treated for idiopathic GH deficiency (IGHD; 46.9%), organic GHD (10.0%), small for gestational age (SGA; 9.5%), Turner syndrome (TS; 9.2%), idiopathic short stature (ISS; 8.2%), and others (16.2%). Median rhGH treatment duration was 2.7 years and observation 3.1 years. SAEs occurred in 3.7% of patients and death in 0.4%. The most common SAEs were recurrence of craniopharyngioma (n = 151), neoplasm (n = 99), and cancer (n = 91); and scoliosis (n = 91). Median first-year delta height-SDS (Prader) in prepubertal patients was 0.66 (IGHD), 0.55 (ISS), 0.58 (TS), 0.71 (SGA). Median gains in NAH-SDS were 1.79 (IGHD), 1.37 (ISS), and 1.34 (SGA) for boys, and 2.07 (IGHD), 1.62 (ISS), 1.07 (TS), and 1.57 (SGA) for girls. Conclusion Data from KIGS, the largest and longest running international database of rhGH-treated children, show that rhGH is safe and increases short-term height gain and adult height across GHD and non-GHD conditions.

Mathematical models have been applied in prediction of growth hormone treatment effectiveness in children since the end of 1990s. Usually they were multiple linear regression models; however, there are also examples derived by empirical non-linear methods. Proposed solution consists in application of machine learning technique – artificial neural networks – to analyse this problem. This new methodology, contrary to previous ones, allows detection of both linear and non-linear dependencies without assuming their character a priori. The aims of this work included: development of models predicting separately growth during 1st year of treatment and final height as well as identification of important predictors and in-depth analysis of their influence on treatment’s effectiveness. The models were derived on the basis of clinical data of 272 patients treated for at least 1 year, 133 of whom have already attained final height. Starting from models containing 17 and 20 potential predictors, respectively for 1st year and final height model, we were able to reduce their number to 9 and 10. Basing on the final models, IGF-I concentration and earlier growth were indicated as belonging to most important predictors of response to GH therapy, while results of GH secretion tests were automatically excluded as insignificant. Moreover, majority of the dependencies were observed to be non-linear, thus using neural networks seems to be reasonable approach despite it being more complex than previously applied methods.

Introduction. Prediction of recombinant human growth hormone (rhGH) therapy effectiveness seems an important issue, especially in situations when diagnosis is problematic. Until now the problem was solved by multiple regression analysis, while here we propose application of artificial neural networks (ANN), particularly multilayer perceptron (MLP), as a novel tool. Material and methods. The analysis was performed on data of 289 patients, treated for at least 2 years due to GH deficiency. First, we automatically classified patients to one of two groups depending on attainment of final height (FH) over or below 10 th centile (2-stage classification). Secondly, we introduced third group for FH below 3 rd centile (3-stage classification). Finally, we predicted attained FH standard deviation score (SDS) in ANN regression model. Results. In 2-stage version MLP networks classified more than 80% of patients correctly. In 3-stage classification, the ratio of right answers was close to 70%. ANN regression model predicted FH SDS with average error of 0.7 SD (4.2 cm), explaining about 45% of its variability. Conclusion. The results of the study are promising and the topic definitely worth further consideration. Due to their characteristics, ANN seem to be par-Słowa kluczowe Sztuczne sieci neuronowe, hormon wzrostu, modelowanie skuteczności leczenia Streszczenie